Reference of 13535-07-4, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 13535-07-4 as follows.
To a solution of (4S)-7-(6-methylpyridin-3-yl)-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3- b][l,4]diazepine (600 mg, 2.378 mmol), triphosgene (706 mg, 2.378 mmol) and triethylamine (1.989 mL, 14.27 mmol) in tetrahydrofuran (THF) (15 mL) stirred under nitrogen at room temperature for 30 min was added 5-ethylpyrazin-2-amine (879 mg, 7.13 mmol). The reaction mixture was stirred at 70 C for 16 h and cooled to room temperature and then the reaction mixture was poured in to water and extracted with EtOAc (3 X 15 mL). The combined organic layers were washed with water, brine solution, dried over sodium sulfate and evaporated to give crude compound (TLC eluent: 5% MeOH in DCM: RrO. l; UV active). The crude compound was purified by column chromatography using Neutral Alumina and eluted with 30%EtO Ac/Pet ether to afford pure (4S)-N-(5- ethylpyrazin-2-yl)-7-(6-methylpyridin-3-yl)-3,4-dihydro-l,4-methanopyrido[2,3- b][l,4]diazepine-5(2H)-carboxamide (383 mg, 0.953 mmol, 40.1 % yield), LCMS (m/z): 402.3 [M+H]+.1H NMR (400 MHz, CDC13): delta ppm 13.65 (s, 1 H) 9.41 (d, J=1.53 Hz, 1 H) 9.11 (d, J=2.19 Hz, 1 H) 8.41 (dd, J=8.22, 2.52 Hz, 1 H) 8.22 (d, J=1.32 Hz, 1 H) 7.61 (d, J=7.89 Hz, 1 H) 7.40 (d, J=8.11 Hz, 1 H) 7.32 (d, J=8.11 Hz, 1 H) 5.70 (dd, J=6.03, 3.18 Hz, 1 H) 3.34 – 3.13 (m, 3 H) 3.02 (dd, J=12.06, 3.29 Hz, 1 H) 2.83 (q, J=7.53 Hz, 2 H) 2.64 (s, 3H) 2.40-2.34 (m, 1 H) 2.15 – 2.03 (m, 1 H) 1.33 (t, J=7.56 Hz, 3 H).
According to the analysis of related databases, 13535-07-4, the application of this compound in the production field has become more and more popular.
Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; ELLIS, James Lamond; EVANS, Karen Anderson; FOX, Ryan Michael; MILLER, William Henry; SEEFELD, Mark Andrew; (766 pag.)WO2016/79709; (2016); A1;,
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